3,4-dihydro-4,4-dimethyl-2H-pyran-2-one, an insecticide intermediate

ABSTRACT

Processes for producing a (1α, 4α, 5α)-6,6-dimethyl-4-halo-substituted methyl-3-oxabicyclo[3.1.0]hexan-2-one and its novel intermediates from known and inexpensive starting materials are described and exemplified.

This application is a continuation of application Ser. No. 662,547,filed 10/19/84, now abandoned, which is a continuation of Ser. No.341,372, filed 1/21/82, now abandoned, which is a division ofapplication Ser. No. 162,292, filed 6/23/80, now U.S. Pat. No. 4,342,694issued 8/3/82, which s a division of application Ser. No. 090,223, filed11/1/79, issued 11/25/80 as U.S. Pat. No. 4,235,780.

The present invention relates to (1) the preparation of a (1α, 4α,5α)-6,6-dimethyl-4-halosubstituted-methyl-3-oxabicyclo[3.1.0]hexan-2-one, referred tohereinafter as halomethyl bicyclic lactone, to (2) novel intermediatesfor production of the halomethyl bicyclic lactone, and to (3) variousnovel process steps by which the intermediates and the halomethylbicyclic lactone are prepared from known and inexpensive startingmaterials.

The halomethyl bicyclic lactone is a useful intermediate for theproduction of insecticidalcis-3-(2,2-dihaloethenyl)-2,2-dimethylcyclopropanecarboxylate orcis-3-(2-halo-2-trihalomethylethenyl)-2,2-dimethylcyclopropanecarboxylates.An alternate process for preparing the halomethyl bicyclic lactone andits use as an insecticide intermediate is described in copending U.S.Ser. No. 000,736, filed Jan. 3, 1979.

A process for the production of a trihalomethyl bicyclic lactone isdisclosed in Belgian Pat. No. 868,445, published Dec. 27, 1978. Theprocess, illustrated by the chemical equations below, involves reactingthe corresponding hydroxy bicyclic lactone, caronaldehydic acid, with ahaloform, then cyclo-dehydrating the acid formed to produce thetrihalomethyl bicyclic lactone.

Belgian Pat. No. 868,445 ##STR1##

The disclosed process and intermediates of the Belgian patent differfrom the compounds and process of the present invention.

Various processes for preparing caronaldehydic acid, the hydroxybicyclic lactone starting material in the process of the Belgian patent,are known in the art and are exemplified by the following chemicalequations.

U.S. Pat. No. 3,723,469 ##STR2## U.S. Pat. No. 4,132,717 ##STR3##

A feature common to the processes shown above for producing the bicyclicstructure of caronaldehydic acid is the use of a cyclopropane derivativeas starting material upon which the second ring is subsequently built.In the present invention, a cyclopropane ring is not formed until thelast step in the overall process to a bicyclic lactone.

In accordance with the present invention there are provided novelcompounds having the formulas ##STR4## and processes for preparing thesecompounds.

The following definitions are applicable in this application: "lower",as applied to an alkyl or alkoxy group, means having 1-6 carbon atoms,preferably 1-4 carbon atoms; "halo" or "halogen" means a fluorine,chlorine, or bromine atom which may be independently selected; and"aryl" means a phenyl radical which may be substituted with one or morehalogen atoms and/or lower alkyl groups. These definitions applythroughout the specification and claims except where a contrary meaningis clearly indicated.

One aspect of the invention comprises a novel class of3,3-dimethylpentanoyl derivatives of the formula ##STR5## wherein R¹ isa hydroxy group or the group --OR where R is a lower alkyl radical;

R² is a hydrogen or chlorine atom; and

R³ is the group --SR⁴ where R⁴ is an aryl radical, preferably phenyl;

or

R² and R³ are taken together and are an oxygen atom.

Other composition aspects of this invention comprise compounds of theformulas ##STR6## X¹ and X² are the same or different and each is anindependently selected halogen atom, a trichloromethyl group, or atrifluoromethyl group, and Y¹ and Y² are independently bromine, orchlorine atoms with the proviso that Y¹ is a bromine atom when at leastone of X¹, X², and Y² is a bromine atom. In preferred compounds offormula III X¹ is a bromine or chlorine atom, particularly a chlorineatom, and X² is the same as X¹ or is a trifluoromethyl group.

Compounds of the formulas I, II, and III are useful intermediates forthe production of a halomethyl bicyclic lactone of the formula ##STR7##wherein Y², X¹ and X² are as defined for the compounds of formula III.

The process embodiment of the present invention relates to processes forthe production of the compounds of formulas I, II, III and IV, and anoverall process for the production of compounds of formula IV in whichthe compounds of formulas I, II and III are intermediates.

The overall process comprises six basic steps and an alternate step. Theoverall process, each step including the alternate step, and allcombinations of successive steps represent individual processes of theinvention. These processes are illustrated by the chemical equationsbelow. The product of each step, except step VI, is a novel compositionof matter of the present invention. Each is a compound of formula I, IIor III, and is numbered accordingly. ##STR8##

STEP I

In one process aspect, step I above, the intermediate of formula I(a), alower alkyl 3,3-dimethyl-5-arylthiopentanoate, is produced by theaddition reaction of an aryl mercaptan and a lower alkyl3,3-dimethyl-4-pentenoate. ##STR9## R is lower alkyl, conveniently ethylor methyl. R⁴ is an aryl group, preferably phenyl.

An initiator is required in step I to initiate the reaction, which ispresumably a free radical addition reaction. Suitable initiators includelight and free radical initiators such as acyl peroxides. Benzoylperoxide has been found to be desirable and highly effective. When anacyl peroxide is employed, satisfactory results are obtained when theamount of peroxide used is in the range of about 0.5 mole % to about 6mole % based on the pentenoate substrate. The acyl peroxide mayconveniently be introduced into the reaction vessel in a single additionor portionwise in several additions throughout the course of thereaction. The use of light as an initiator generally gives poor resultswhen it is employed alone. However, the use of light in in conjunctionwith another initiator, particularly benzoyl peroxide, generally resultsin higher yields of the addition product than obtained with eitherinitiator alone. An incandescent light bulb, advantageously of at least50 watts, preferably of at least 100 watts, may be utilized as the lightsource.

The step I reaction is conducted at an elevated temperature, usually inthe range of about 80° C. to 140° C., preferably 100° C. to 130° C.Under these conditions, a reaction time of from one to five days,generally four or five days, is usually sufficient. A solvent isgenerally not required in the reaction, but solvents which do notadversely affect the reaction or the product may be employed.

STEP II

A second process aspect of the present invention relates to step II inthe overall process shown above. This step is illustrated by thechemical equation below wherein R and R⁴ are as defined for step I.##STR10##

In this aspect, the lower alkyl 3,3-dimethyl-5-arylthiopentanoate I(a)is chlorinated to give the corresponding 5-arylthio-5-chloro compoundI(b). Many chlorinating agents are known to be capable of chlorinatingan alkyl aryl thioether in the α-position of the alkyl group and areexpected to be suitable for use here. The use of1-chloro-2,5-pyrrolidinedione is especially desirable since it usuallydoes not require extensive product purification during workup.

The chlorination reaction is conducted at a temperature in the range ofabout -20° C. to 50° C., preferable 0° C. to 25° C., in an inertsolvent. A particularly useful solvent is tetrahydrofuran or carbontetrachloride. Other solvents which do not adversely affect the reactionare also suitable, and include dioxane, 1,2-dimethoxyethane, andchloroform. Generally, 4-8 ml of solvent for each gram of compound I(a)to be chlorinated is sufficient. With 1-chloro-2,5-pyrrolidinedione, thereaction is adequately complete within 2-9 hours, usually 3-4 hours,when the reaction temperature is in the range of about 5° C. to 20° C.

If the product of step II is to be carried forward in step III of thepresent overall process, it is usually not necessary that it be isolatedand purified. Mere filtering of the step II reaction mixture affords asolution of the chlorinated product adequately pure for use per se inthe step III reaction.

STEP III

Step III, illustrated by the chemical equation below, is a third processaspect of the present invention and relates to a process for producing alower alkyl 3,3-dimethyl-5-oxopentanoate, I(c), by hydrolysis of thecorresponding 5-arylthio-5-chloro derivative I(b). ##STR11## R and R⁴are as defined for step I.

The hydrolysis is effected in the presence of cupric oxide, cupricchloride, and water. Advantageously, equal parts by weight of cupricoxide and cupric chloride are used with from about 0.9 to 4 moles,preferably 1 mole, of cupric oxide being employed for each mole ofsulfide to be hydrolyzed. At least one molar equivalent of water isrequired for the hydrolysis, based on the amount of material to behydrolyzed. The use of an excess of water does not appear to criticallyinterfere with the reaction.

The step III reaction is conducted in the presence of a solvent, whichshould be at least partially water soluble. Suitable solvents includediethyl ether, 1,2-dimethoxyethane, dioxane, tetrahydrofuran, acetone,and numerous other water soluble or partially water soluble solvent.Particularly useful solvents are acetone and tetrahydrofuran.

The hydrolysis can be conducted over a wide temperature range but ispreferably conducted at a temperature in the range of from about 10° C.to 30° C., conveniently at room temperature.

STEP IV

A fourth process aspect of this invention relates to step IV of theoverall process and provides for the production of3,4-dihydro-4,4-dimethyl-2H-pyran-2-one, the compound of formula II, bycyclization of a compound of formula I(c). R is as defined for step I.##STR12##

To effect the cyclization a cyclizing agent, preferably phosphorylchlorine, is required. While cyclizing agents such as benzoyl chloride,para-toluenesulfonic acid, para-toluenesulfonic acid hydrate, or amixture of para-toluenesulfonic acid and acetic anhydride can be used,their use frequently favors a competing reaction in which a di-loweralkyl 3,3-dimethyl-1,5-dicarboxylate is formed. The diester by-productis formed to a lesser extent when phosphoryl chloride is used. Bestresults are obtained when from about 0.5 to 1.5 moles of cyclizing agentare used for each mole of I(c) to be cyclized.

The cyclization is conducted in the presence of a solvent, preferablysulfolane. Other solvents such as benzene, toluene, and dioxane can beused, but their use generally results in a lower yield of cyclizedproduct II, and the formation of considerable diester by-product.

The reaction is conducted at elevated temperature, preferably in therange of about 110° C. to 225° C., more preferably 180° C. to 210° C.Under these temperature conditions a reaction time of 1 to 2 hours isusually sufficient.

ALTERNATE STEP IV

It will be evident to those skilled in the art that the dihydropyranoneII can also be produced from 3,3-dimethyl-5-oxopentanoic acid, I(d), anovel and hitherto unavailable compound now accessible by hydrolysis ofthe 5-oxopentanoate I(c). This alternate route to compound II, whichcomprises the steps of (a) hydrolyzing the lower alkyl3,3-dimethyl-5-oxopentanoate I(c) to give 3,3-dimethyl-5-oxopentanoicacid, I(d) and then (b) cyclizing the 3,3-dimethyl-5-oxopentanoic acidto form 3,4-dihydro-4,4-dimethyl-2H-pyran-2-one, II, is a fifth processaspect of this invention. R is lower alkyl in the formula below.##STR13## (a) Hydrolysis of the lower alkyl 3,3-dimethyl-5-oxopentanoateI(c) to give 3,3-dimethyl-5-oxopentanoic acid, I(d), is effected in acidor base, at a temperature advantageously in the range of about 20° C. to50° C.

In a particularly effective method of hydrolysis, the ester I(c) issubjected to saponification using sodium hydroxide or potassiumhydroxide, followed by acidification of the resulting sodium orpotassium salt to form the free acid I(d). The reaction is facilitatedby use of a mixture of methanol or ethanol and water for dissolution ofthe alkali metal hydroxide and the ester. If the hydrolysis is conductedat about 25° C., a reaction time of about 1 to 4 days, usually 1 to 2days, is generally sufficient.

(b) For cyclization of the free acid I(d), a cyclizing agent, preferablythionyl chloride, is required. Other suitable cyclizing agents includephosphoryl chloride, benzoyl choride, para-toluenesulfonic acid,para-toluenesulfonic acid hydrate, and a mixture of para-toluenesulfonicacid and acetic anhydride. The reaction is conducted at a temperature inthe range of about 25° C. to 150° C., usually about 80° C. to 115° C.,in an inert solvent, for example an aromatic hydrocarbon such asbenzene, toluene or xylene. Typically, a solution of the acid I(d) andthoionyl chloride (about 1 to 2 moles for each mole of I(d) issufficient) in benzene is heated under reflux for up to about 24 hours,usually 5 to 8 hours.

STEP V

A sixth process aspect, step V of the overall process, provides for theproduction of the compound of formula III, a 5-bromo- orchloro-3,4,5,6-tetrahydro-4,4-dimethyl-6-halosubstituted-methyl-2H-pyran-2-one, by a regiospecific free radicaladdition of a halomethane, Y¹ CY² X¹ X², across the double bond of thedihydropyranone II. In the formulas below X¹ and X² are the same ordifferent and each is an independently selected halogen atom, atrichloromethyl group, or a trifluoromethyl group, and Y¹ and Y² areindependently bromine or chlorine atoms with the proviso that Y¹ is abromine atom when at least one of X¹, X², and Y² is a bromine atom.##STR14##

The reaction is conducted in the presence of an initiator selected froman acyl peroxide, light, and an acyl peroxide and light. Benzoylperoxide is a preferred acyl peroxide. The light source may be anincandescent light bulb, advantageously of at least 50 watts, preferablyof at least 100 watts. When an acyl peroxide is employed, it isadvantageously used in an amount in the range of about 25 to 100 mole %based on the amount of the dihydropyranone II to be converted. It isalso advantageous to add the acyl peroxide to the reaction vessel inseveral portions throughout the course of the reaction rather than in asingle addition at the outset. Other free radical initiators such asazobisisobutyronitrile appear to be ineffective initiators for thereaction, particularly when a short reaction time is employed.

The use of a solvent, although generally not required, is desirable. Alarge molar excess of the halomethane may be used and will serve as thesolvent. Other solvents which do not adversely affect the reaction orreaction product, for example, acetonitrile, alcohols,dimethylformamide, aliphatic hydrocarbons, aromatic hydrocarbons, andthe like, are also suitable.

The reaction is conducted at an elevated temperature, preferably at atemperature in the range of about 50° C. to 200° C., more preferably atfrom 60° C. to 125° C.

The regiospecific addition of the free radical .CY² X¹ X² to C-6 of thedihydropyranone ring rather than to C-5 is surprising. It is known inthe art that free radicals with the unpaired electron α to an OR group(C-6 of the dihydropyranone may be considered α to an OR group) haveincreased stability. See J. March, Advanced Organic Chemistry, SecondEdition, P. 632, McGraw-Hill Book Co., New York, 1977, 1968. One wouldthus expect addition of .CY² X¹ X² to occur at C-5, resulting in anunpaired electron at C-6 which could be stabilized by resonance:##STR15##

A possible explanation for the unexpected course of the reaction is thataddition of .CY² X¹ X² to C-5 is sterically hindered by the presence ofthe gem-dimethyl group at C-4, and/or the expected resonancestabilization of an unpaired electron at C-6 because of its positionadjacent to oxygen with its unbonded electrons, is diluted by theelectron withdrawing carbonyl group at C-2 thereby minimizing itseffect. It is known that steric hindrance can play a role in freeradical addition, for example, the addition of a trichloromethyl radicalto the exo side of norbornene; See "Steric Control in the Free RadicalAddition of Carbon Tetrachloride to Norbornenes," C. L. Osborn et al.,J. Am. Chem. Soc., 90, 5806 (1968). However, no reference has been founddirectly comparing steric effects and resonance stabilization in freeradical addition reactions. Thus, the regiospecific addition of .CY² X¹X² to C-6 of the dihydropyranone is unexpected since one could not havepredicted in advance which course the reaction might take.

STEP VI

A seventh process aspect, step VI of the overall process, provides forthe preparation of the halomethyl bicyclic lactone IV bydehydrohalogenation of the 5-bromo- or chloro-tetrahydropyranone offormula III, bringing about ring closure to form the bicyclic lactone.In the formulas below Y¹, Y², X¹, and X² are as defined for step V.##STR16##

The dehydrohalogenation of III to give IV is effected by base. Effectivebases include alkali metal hydrides and alkali metal alkoxides,particularly t-alkoxides such as the sodium or potassium salt oft-butanol or t-pentanol. Use of a sterically hindered base such as asodium or potassium t-alkoxide, or a base that is an effective protonabstractor but not a particularly effective nucleophile such as sodiumhydride is desirable and generally results in a higher yield of thehalomethyl bicyclic lactone IV. Straight chain alkoxides will alsoeffect the desired conversion but will usually enter into a competingreaction involving the C-2 carbonyl group of the substrate; the yield ofdesired product IV being reduced in proportion to the extent to whichthe competing reaction operates. The product of the competing reactionis an epoxide, exemplified by compound V in the following chemicalequation which illustrates the reaction when sodium methoxide isemployed as the base. ##STR17##

The reaction is conducted in the presence of a solvent, suitablynon-hydroxylic, for example, an ether of 4-6 carbon atoms such asdiethyl ether, dioxane, dimethoxy ethane or tetrohydrofuran, an aromatichydrocarbon of 6 to 10 carbon atoms such as benzene or toluene, or analiphatic hydrocarbon of 5 to 10 carbon atoms such as pentane, hexane orheptane. The use of tetrahydrofuran or toluene is preferred.

The dehydrohalogenation proceeds facilely at a temperature in the rangeof about -40° C. to 30° C. The preferred temperature range is about -10°C. to 10° C.

The present invention is illustrated in greater detail by the followingexamples. Temperatures are in degree Celsius and pressures are in mm Hgand/or Pa. Unless otherwise specified, concentration of liquid volumewas carried out under the reduced pressure produced by a wateraspirator. Purity determinations were made by gas liquid phasechromatography (glpc). Tetramethylsilane was employed as an internalstandard for the nmr spectra. In reporting the nmr data theabbreviations have the following significance: s, singlet; d, doublet;t, triplet; q, quartet; m, multiplet. Any of the abbreviations may bepreceded by b for broad or d for double, for example, b.s., broadsinglet.

Example 1 illustrates the preparation of a compound of formula I(a) bythe process of step I.

EXAMPLE 1 Preparation of ethyl 3,3-dimethyl-5-phenylthiopentanoate

A mixture of 60.0 g (0.384 mole) of ethyl 3,3-dimethyl-4-pentenoate and90.0 g (0.817 mole) of benzenethiol was irradiated with a 100 wattincandescent light bulb at 120°-130° C. for 4 days. Benzoyl peroxide(1.8 g, 0.0074 mole) was added to the reaction vessel in 300 mgincrements at various times throughout the 4-day irradiation period fora total of six such additions. Distillation of the reaction mixture gave102.3 g (96% yield) of ethyl 3,3-dimethyl-5-phenylthiopentanoate, 96.3%purity (glpc) hp 130° C./27 Pa (0.2 mm Hg).

Methyl 3,3-dimethyl-5-phenylthiopentanoate, 97.1% purity (glpc), bp 130°C./40 Pa (0.3 mm Hg), was prepared by the procedure of Example 1 in 92%yield.

Example 2 illustrates the preparation of a compound of formula I(b) bythe process of step II.

EXAMPLE 2 Preparation of ethyl5-chloro-3,3-dimethyl-5-phenylthiopentanoate

To a solution of 1.06 g (3.09 mmol) of ethyl3,3-dimethyl-5-phenylthiopentanoate in 10 mL of carbon tetrachloride wasadded to 590 mg (4.4 mmol) of 1-chloro-2,5-pyrrolidinedione, and themixture was stirred at room temperature for 2 hours. The mixture wasfiltered, and the filtrate concentrated to give ethyl5-chloro-3,3-dimethyl-5-phenylthiopentanoate as an oil. The product wasused without further purification in the reaction described in Example 3below.

NMR Data (CDCl₃): δ(ppm): 1.10 (6H, s), 1.20 (3H, t), 2.10 (2H, d), 2.25(2H, s), 4.02 (2H, q), 5.23 (1H, t), 7.00-7.53 (5H, m).

Example 3 illustrates the preparation of a compound of formula I(c) bythe process of step III.

EXAMPLE 3 Preparation of ethyl 3,3-dimethyl-5-oxopentanoate from ethyl5-chloro-3,3-dimethyl-5-phenylthiopentanoate

The crude ethyl 5-chloro-3,3-dimethyl-5-phenylthiopentanoate fromExample 2 was dissolved in 15 mL of acetone, and the solution was addedto a mixture of 1.2 g (8.9 mmol) of cupric chloride and 1.2 g (15 mmol)of cupric oxide in 15 mL of acetone and 0.6 mL of water. The mixture wasstirred at room temperature for 30 minutes, filtered, and the filtrateconcentrated to give a residue. The residue was dissolved in methylenechloride, and the solution washed successively with an aqueous sodiumbicarbonate solution and an aqueous solution of sodium chloride. Theorganic layer was separated, dried over anhydrous magnesium sulfate,filtered, and the filtrate concentrated to give 1.0 g of ethyl3,3-dimethyl-5-oxopentanoate.

NMR Data (CCl₄): δ(ppm): 1.11 (6H, s), 1.23 (3H, t), 2.32 (2H, s), 2.45(2H, b.s.), 4.05 (2H, g), 9.72 (1H, b.s.).

Examples 4 and 5 illustrate the preparation of a compound of formulaI(c) from the corresponding compound of formula I(a) by the processes ofsteps II and III conducted successively.

EXAMPLE 4 Preparation of ethyl 3,3-Dimethyl-5-oxopentanoate from ethyl3,3-dimethyl-5-phenylthiopentanoate without purification of theintermediate ethyl 5-chloro-3,3-dimethyl-5-phenylthiopentanoate

A mixture of 30.0 g (0.113 mole) of ethyl3,3-dimethyl-5-phenylthiopentanoate and 16.2 g (0.121 mole) of1-chloro-2,5-pyrrolidinedione in 150 mL of carbon tetrachloride wasstirred at 10°-20° C. for 3 hours. The mixture was filtered, and thefiltrate concentrated at room temperature to give a residue.

The residue was added to a mixture of 10 g (0.074 mole) of cupricchloride and 10 g (0.126 mole) of cupric oxide in 150 mL of acetone and6 mL of water. The reaction mixture was stirred for 1 hour at roomtemperature, then filtered and the filtrate concentrated to give aresidue. The residue was dissolved in ether, washed with an aqueoussolution of sodium chloride, concentrated, and the concentrate subjectedto distillation to give 15.4 g (72% yield) of ethyl3,3-dimethyl-5-oxopentanoate, 91% purity (glpc), bp 50°-60° C./40 Pa(0.3 mm Hg).

Methyl 3,3-dimethyl-5-oxopentanoate was prepared from methyl3,3-dimethyl-5-phenylthiopentanoate in the manner of Example 4, bp93°-97° C./2130 Pa (16 mm Hg), 86%-90% purity, 52% yield.

EXAMPLE 5 Preparation of ethyl 3,3-dimethyl-5-oxopentanoate from ethyl3,3-dimethyl-5-phenylthiopentanoate without isolation of theintermediate ethyl 5-chloro-3,3-dimethyl-5-phenylthiopentanoate

A mixture of 5.30 g (0.020 mole) of ethyl3,3-dimethyl-5-phenylthiopentanoate and 2.95 g (0.022 mole) of1-chloro-2,5-pyrrolidinedione in 30 mL of tetrahydrofuran was stirred atroom temperature for 2.5 hours, then filtered.

To the filtrate were added 1 mL of water, 3 g (0.038 mole) of cupricoxide, and 3 g (0.022 mole) of cupric chloride. The mixture was stirredfor 1 hour at room temperature, filtered, and the filtrate concentrated.The resulting residue was dissolved in methylene chloride and washedwith water. The organic layer was concentrated and subjected to columnchromatography on silica gel, eluting with hexane-ethyl acetate gradientmixtures, to give 1.50 g (44% yield) of ethyl3,3-dimethyl-5-oxopentanoate.

Examples 6 and 7 illustrate preparation of the compound of formula II bythe process of step IV.

EXAMPLE 6 Preparation of 3,4-dihydro-4,4-dimethyl-2H-pyran-2-one intoluene

A solution of 11.16 g (0.065 mole) of ethyl 3,3-dimethyl-5-oxopentanoateand 11.2 g (0.073 mole) of phosphoryl chloride in 90 mL of toluene washeated under reflux for 14 hours. The mixture was diluted with ether,washed with an aqueous solution of sodium bicarbonate, dried overanhydrous magnesium sulfate, filtered, and the filtrate concentrated togive, after distillation, 3.29 g (40% yield) of3,4-dihydro-4,4-dimethyl-2H-pyran-2-one, bp 105°-110° C./2670 Pa (20 mmHg).

NMR Data (CDCl₃): δ(ppm): 1.10 (6H, s), 2.47 (2H, s), 5.12 (1H, d, J=6Hz), 6.33 (1H, d, J=6 Hz).

EXAMPLE 7 Preparation of 3,4-dihydro-4,4-dimethyl-2H-pyran-2-one insulfolane

A solution of 16.98 g (0.10 mole at 93% purity) of ethyl3,3-dimethyl-5-oxopentanoate and 9.44 g (0.062 mole) of phosphorylchloride in 10 g of sulfolane was added to 250 g of sulfolane and thewhole heated to 200° C. in an oil bath during 50 minutes. The reactionmixture was stirred at 200° C. for 1 hour, then subjected todistillation to give 9.71 g of 3,4-dihydro-4,4-dimethyl-2H-pyran-2-onein 2 fractions: fraction 1, 7.49 g, bp 55° C./400 Pa (3 mm Hg), 95.9%purity (glpc); fraction 2, 2.22 g, bp 55°-120° C./400 Pa, 71.1% purity(glpc).

Example 8 illustrates preparation of the compound of formula II by theprocess of alternate step IV. The preparation of the compound of formulaI(d), 3,3-dimethyl-5-oxopentanoic acid, is illustrated in Example 8(a).

EXAMPLE 8 Preparation of 3,4-dihydro-4,4-dimethyl-2H-pyran-2-one

a. Hydrolysis of ethyl 3,3-dimethyl-5-oxopentanoate

To a solution of 1.50 g (8.71 mmol) of ethyl3,3-dimethyl-5-oxopentanoate in 50 mL of methanol and 1 mL of water wasadded 1.0 g (17.8 mmol) of potassium hydroxide. The reaction mixture wasstirred at room temperature for 411/2 hours. The reaction mixture wasdiluted with water and then made acidic by the addition of aqueoushydrochloric acid. The resulting solution was extracted with methylenechloride repeatedly. The combined organic layer was washed with anaqueous solution of sodium chloride and dried over anhydrous magnesiumsulfate. Removal of the solvent afforded 1.05 g of3,3-dimethyl-5-oxopentanoic acid, 84% crude yield. The nmr spectrum wasconsistent with the proposed structure.

b. Cyclization of 3,3-dimethyl-5-oxopentanoic acid

A solution of 1.05 g (7.28 mmol) of crude 3,3-dimethyl-5-oxopentanoicacid (from Example 8a) and 1 g (8.4 mmol) of thionyl chloride in 10 mLof benzene was heated under reflux for 62/3 hours. The reaction mixturewas concentrated to give 3,4-dihydro-4,4-dimethyl-2H-pyran-2-one. Thenmr spectrum was consistent with the proposed structure.

Examples 9 and 10 illustrate the preparation of a compound of formulaIII by the process of Step V. Example 10 also showsazobisisobutyronitrile to be an ineffective initiator for the additionreaction under the conditions employed.

EXAMPLE 9 Preparation of5-bromo-3,4,5,6-tetrahydro-4,4-dimethyl-6-trichloromethyl-2H-pyran-2-one

a. Use of light as the initiator

A gently refluxing mixture of 2.10 g (16.3 mmol) of of3,4-dihydro-4,4-dimethyl-2H-pyran-2-one (98% purity) and 10 g (50 mmol)of bromotrichloromethane was irradiated for 6 days. The light source wasa 100 watt incandescent light bulb. The reaction mixture was subjectedto column chromatography on silica gel eluting with a 10:1 mixture ofhexane:ethyl acetate to give 2.79 g (53% yield) of5-bromo-3,4,5,6-tetrahydro-4,4-dimethyl-6-trichloromethyl-2H-pyran-2-one.The product was purified by sublimation, mp 98.5°-99.5° C.

NMR Data (CDCl₃): δ(ppm): 1.23, 1.25 (ss, 6H), 2.67 (2H, bs), 4.12 (1H,d, J=6 Hz), 5.28 (1H, d, J=6 Hz).

b. Use of benzoyl peroxide as the initiator

A mixture of 1.0 g (7.93 mmol) of3,4-dihydro-4,4-dimethyl-2H-pyran-2-one and 6.29 g (31.7 mmol) ofbromotrichloromethane was heated to 100° C. Heating was maintained at100° C. for 12 hours. During this time 600 mg (2.48 mmol) of benzoylperoxide was added in six 100 mg portions; a 100 mg portion being addedapproximately every 2 hours. The reaction mixture was cooled and placedon a silica gel packed chromatography column. Elution with 20:1hexane:ethyl acetate mixture afforded 1.45 g, 56% yield, of5-bromo-3,4,5,6-tetrahydro-3,3-dimethyl-6-trichloromethyl-2H-pyran-2-one.

EXAMPLE 10 Preparation of5-chloro-3,4,5,6-tetrahydro-4,4-dimethyl-6-trichloromethyl-2H-pyran-2-one

To a solution of 2.10 g (0.016 mole) of3,4-dihydro-4,4-dimethyl-2H-pyran-2-one in 6.5 g (0.042 mole) of carbontetrachloride was added 100 mg of azobisisobutyronitrile (AIBN), and thereaction mixture stirred at room temperature for 11/2 hours. Analysis ofthe reaction mixture by glpc indicated no adduct had formed. Anadditional 100 mg of AIBN was added and the temperature was raised to80° C. and maintained at that level for 21/4 hours. Analysis by glpcshowed the desired adduct still had not formed.

Benzoyl peroxide was added in 100 mg or 200 mg portions several times aday while the reaction mixture was heated under reflux for 6 days. Thetotal amount of benzoyl peroxide added was 3.7 g (0.015 mole).

The reaction mixture was cooled and placed on a silica gel packedchromatography column. Elution with a 10:1 hexane:ethyl acetate mixturegave 3.10 g, 70% yield, of5-chloro-3,4,5,6-tetrahydro-4,4-dimethyl-6-trichloromethyl-2H-pyran-2-oneas an oil which crystallized upon standing. Recrystallization frompentane afforded the product as white crystals, mp 83°-84° C.

Analysis for C₈ H₁₀ Cl₄ O₂ : Calc'd: C, 34.32; H, 3.60; Cl, 50.65;Found: C, 34.65; H, 3.59; Cl, 50.51.

Example 11 illustrates preparation of the trihalomethyl bicyclic lactone(1α, 4α,5α)-6,6-dimethyl-4-trichloromethyl-3-oxabicyclo[3.1.0]hexan-2-one.

EXAMPLE 11 Preparation of (1α, 4α,5α)-6,6-dimethyl-4-trichloromethyl-3-oxabicyclo[3.1.0 ]hexan-2-one

A solution of 0.4 g (1.43 mmol) of5-chloro-3,4,5,6-tetrahydro-4,4-dimethyl-6-trichloromethyl-2H-pyran-2-onein 2 mL of tetrahydrofuran was added to a suspension of 0.27 g (2.8mmol) of sodium tert-butoxide in 2 mL of tetrahydrofuran at 0° C. Themixture was stirred at 0° C. for 2 hours, diluted with an aqueoussolution of ammonium chloride, and the whole extracted with methylenechloride. The methylene chloride extract was dried over anhydrousmagnesium sulfate and then concentrated. The residue was placed on asilica gel packed chromatography column. Elution with a 100:3hexane:ethyl acetate mixture gave 0.29 g, 69% yield (1α, 4α,5α)-6,6-dimethyl-4-trichloromethyl-3-oxobicyclo[3.1.0]hexan-2-one, 83%purity. The proposed structure was confirmed by comparison of the nmrspectrum and glpc retention time with those obtained for an authenticsample prepared by a different method. Analysis by glpc also showed thepresence of 13% unreacted5-chloro-3,4,5,6-tetrahydro-4,4-dimethyl-6-trichloromethyl-2H-pyran-2-one.

We claim:
 1. The compound of 3,4-dihydro-4,4-dimethyl-2H-pyran-2-one. 